Field of the Invention
The present invention relates to methods and compositions for treating, ameliorating, or preventing a disease, disorder, or condition in a subject by introducing into the subject a therapeutic gene switch construct that controls expression of one or more therapeutic products. In a further embodiment, the present invention relates to methods and compositions for treating, ameliorating, or preventing a disease, disorder, or condition in a subject by introducing into the subject a “bioreactor,” a therapeutic implant composed of a cell or cells that secrete a therapeutic protein. A bioreactor may be immuno-isolated by encapsulation or non-immunoisolated. In particular embodiments, the bioreactor comprises a therapeutic gene switch construct.
Background of the Invention
The concept of treating or preventing a disease in a subject through introduction of a polynucleotide encoding a therapeutic molecule, e.g., a therapeutic polypeptide or therapeutic polynucleotide into cells of the subject, or introducing into the subject modified cells engineered to secrete the therapeutic molecule has been in existence for many years. Several difficulties in the practical aspects of the concept have hindered progress towards successful therapies. Direct introduction of genetic material into a subject to be treated presents difficulties such as: safety of delivery, obtaining sufficient expression levels of the therapeutic product for a sufficient period of time, limiting expression of the therapeutic product to desired cells, and maintaining the ability to modulate or pulse the expression of the therapeutic product, including the ability to turn off expression of the therapeutic product if it is no longer needed. Cell based therapies are subject to rejection via the subject's immune response, therefore immuno-isolation strategies such as cell encapsulation methods have been developed to increase the longevity of implanted cells and allow use of xenogeneic cells, i.e., cells from a different species. Current encapsulated and non-encapsulated cell therapies are engineered to secrete the therapeutic protein constitutively. Once implanted, protein secretion can not be regulated. To improve the safety and clinical application of direct or cell-mediated bioreactor therapeutic protein delivery it would be advantageous to be able to turn off the protein production or regulate the rate at which protein production occurs.
Thus, there is a need in the art for new therapeutic methods and compositions that provide these desired characteristics.